Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response

Myeloid Leukemia, Chronic Clinical Trial

— AFR22  

Official title:

Multicentric Phase II Study to Evaluate Feasibility and Efficacy of Association of Imatinib Mesylate and Zoledronic Acid in Patients With Chronic Myeloid Leukaemia in Cytogenetic Response Without Molecular Response After One Year of Imatinib Mesylate Monotherapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00210119
• Other study ID #: IB2005-25
• Secondary ID: AFR22
• Status: Terminated
• Phase: Phase 2
• Start date: July 12, 2006
• Est. completion date: March 2009

Study information

• Verified date: September 2021
• Source: Institut Bergonié
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Imatinib mesylate is standard treatment of Chronic myeloid leukaemia, complete cytogenetic response is obtained in most of cases but molecular response concerned only a small part of the patients. To increase molecular response ratio we decided to increase imatinib dose to limited resistance to this drug and to add zoledronate for it anti tumoral activity to increase anti leukemic effect. We plan to accrue 37 patients in 5 centers. We will analyse molecular expression of BCR-ABL transcript after 6 months of treatment, safety, duration of response, VEGF expression and LTgd production.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: March 2009
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Inclusion criteria: at registration· Chronic myeloid leukaemia Ph+ confirmed by cytogenetic analysis or BCR-ABL translocation by molecular biology· Chronic phase:-<15% blast cells in blood and 5% in bone marrow-<30% blast cells+promyelocyte cells in blood and bone marrow-<20% basophils in blood->100.000 platelets· Without extra medullar attempt excepted hepatosplenomagalia· First line of treatment· Biology and biochemistry with normal levels· Male or female>18 years old· Signed written consent· ECOG<3At inclusion· Chronic myeloid leukaemia with cytogenetic response without molecular response after one year of treatment by imatinib and BCR-ABL transcript detected by RT-PCR

Exclusion Criteria:

• · Other cancer excepted basocellular or cervix carcinoma · Major surgery in last 2 weeks previous inclusion· Women who are pregnant or breastfeeding (are unable to use an acceptable method to avoid pregnancy of his partner for the entire study period)· Dementia or altered mental status that would prohibit the understanding or rendering of informed consent · Abnormal renal function with creatinine clearance < 30 ml/ minuteAccording to Cockcroft-Gault : CrCl= [[140-age (years)] x weight (kg)]/ [72 x serum creatinine (mg/dL)] {x 0.85 for women}· Chronic myeloid leukaemia in acute phase or in pass to be in acute phase · Treatment with bisphosphonates in last 6 months previous inclusion · Intolerance to bisphosphonates: hypersensitivity, on course dental problem, including tooth or mandibular infection; dental traumatism or recent diagnosis or previous mandibular osteonecrosis, or dental extraction with cicatrisation delay or necessity to set bone evidence · Mandibular surgery in last 6 weeks or planned in the future during treatment (tooth extraction)· Serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy: diabetes, thyroid pathology, neuropsychiatric illness, myocardial infarction or congestive heart failure grade 3-4 according to " New York Heart association"· History of psychiatric or depressive pathology · HIV positivity known · Inclusion in other study investigating antineoplastic molecule in last 30 days previous inclusion

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myeloid Leukemia, Chronic

Intervention

Drug:
• Glivec

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Bordeaux	Bordeaux
France	Institut Bergonié - Centre Régional de Luttre Contre le Cancer de Bordeaux et du Sud Ouest	Bordeaux
France	Centre Hospitalier de Versailles	Le Chesnay
France	Hôpital Edouard Herriot	Lyon
France	Hôpital Archet	Nice
France	Hôpital Saint Louis	Paris
France	Centre Hospitalier Universitaire de Poitiers	Poitiers

Sponsors (2)

Lead Sponsor	Collaborator
Institut Bergonié	Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Molecular Response	A patient is considered to be in molecular response if at least one of the following conditions is observed : - a complete molecular response at 6 months defined by PCR negativation tested on twice; OR; - reduction of BCR-ABL transcript level > 2 Log from the start of from initiation of treatment	6 months
Secondary	Percentage of Participants With a Reduction of BCR-ABL Transcript Level > 4.5 Log From the Start of From Initiation of Treatment	reduction of BCR-ABL transcript level > 4.5 Log from the start of from initiation of treatment	6 months